Clinical and ecological impact of an educational program to optimize antibiotic treatments in nursing homes (PROA-SENIOR): a cluster randomized controlled trial and interrupted time-series analysis.

BACKGROUND: Antimicrobial stewardship programs (ASPs) are recommended in nursing homes (NHs), although data are limited. This study aimed to determine the clinical and ecological impact of an ASP for NHs. METHODS: We performed a cluster randomized controlled trial and a before-after study with interrupted time-series analyses in 14 NHs, for 30 consecutive months from July 2018 to December 2020, in Andalusia, Spain. Seven facilities implemented an ASP with a bundle of five educational measures (general-ASP) and 7 added one-to-one educational interviews (experimental-ASP). The primary outcome was the overall use of antimicrobials, calculated monthly, as defined daily doses (DDD) per 1000 residents-day (DRD). RESULTS: During the ASP implementation, the total mean antimicrobial consumption decreased by 31.2% (-16.72 DRD; p = 0.045) with respect to the pre-intervention period; the overall use of quinolones and amoxicillin-clavulanic acid dropped by 52.2% (p = 0.001) and 42.5% (p = 0.006) respectively; and the overall prevalence of MDRO decreased from 24.7% to 17.4% (p = 0.012). During the intervention period, 12.5 educational interviews per doctor were done in the experimental ASP-group; no differences were found in the total mean antimicrobial use between groups (-14.62 DRD; p = 0.25) and two unexpected SARS-CoV-2 waves affected the participating centers with significant increases in the overall mean use of total antimicrobials of 40% (51.56 DRD; p < 0.0001). CONCLUSION: This study suggests that an ASP for NHs appears to be associated with a decrease in total consumption of antimicrobials and prevalence of MDRO. This trial did not find benefits associated with educational interviews probably due to the COVID-19 pandemic.

Dendritic cell deficiencies persist seven months after SARS-CoV-2 infection.

Severe Acute Respiratory Syndrome Coronavirus (SARS-CoV)-2 infection induces an exacerbated inflammation driven by innate immunity components. Dendritic cells (DCs) play a key role in the defense against viral infections, for instance plasmacytoid DCs (pDCs), have the capacity to produce vast amounts of interferon-alpha (IFN-α). In COVID-19 there is a deficit in DC numbers and IFN-α production, which has been associated with disease severity. In this work, we described that in addition to the DC deficiency, several DC activation and homing markers were altered in acute COVID-19 patients, which were associated with multiple inflammatory markers. Remarkably, previously hospitalized and nonhospitalized patients remained with decreased numbers of CD1c+ myeloid DCs and pDCs seven months after SARS-CoV-2 infection. Moreover, the expression of DC markers such as CD86 and CD4 were only restored in previously nonhospitalized patients, while no restoration of integrin ß7 and indoleamine 2,3-dyoxigenase (IDO) levels were observed. These findings contribute to a better understanding of the immunological sequelae of COVID-19.

SARS-CoV-2 viral load in nasopharyngeal swabs is not an independent predictor of unfavorable outcome.

The aim was to assess the ability of nasopharyngeal SARS-CoV-2 viral load at first patient's hospital evaluation to predict unfavorable outcomes. We conducted a prospective cohort study including 321 adult patients with confirmed COVID-19 through RT-PCR in nasopharyngeal swabs. Quantitative Synthetic SARS-CoV-2 RNA cycle threshold values were used to calculate the viral load in log10 copies/mL. Disease severity at the end of follow up was categorized into mild, moderate, and severe. Primary endpoint was a composite of intensive care unit (ICU) admission and/or death (n = 85, 26.4%). Univariable and multivariable logistic regression analyses were performed. Nasopharyngeal SARS-CoV-2 viral load over the second quartile (≥ 7.35 log10 copies/mL, p = 0.003) and second tertile (≥ 8.27 log10 copies/mL, p = 0.01) were associated to unfavorable outcome in the unadjusted logistic regression analysis. However, in the final multivariable analysis, viral load was not independently associated with an unfavorable outcome. Five predictors were independently associated with increased odds of ICU admission and/or death: age ≥ 70 years, SpO2, neutrophils > 7.5 × 103/µL, lactate dehydrogenase ≥ 300 U/L, and C-reactive protein ≥ 100 mg/L. In summary, nasopharyngeal SARS-CoV-2 viral load on admission is generally high in patients with COVID-19, regardless of illness severity, but it cannot be used as an independent predictor of unfavorable clinical outcome.